This invention relates to therapeutic interference with interactions between cell adhesion proteins and their carbohydrate ligands.
ELAM-1 is an integral membrane adhesion protein. It possesses an extracellular domain including an N-terminal lectin-related segment, an epidermal growth factor related repeat, and multiple complement regulatory protein motifs (Bevilacqua et al., Science 243:1160, 1989; Stoolman et al., Cell 56:907, 1989). ELAM-1 is specifically expressed on the surface of endothelial cells activated by the cytokines IL-1 and tumor necrosis factor (TNF) (Bevilacqua et al., Proc. Natl. Acad. Sci. USA 84:9238, 1987), or the peptide hormone Substance P (Matis et al., J. Invest. Dermatol. 94:492, 1990). It mediates adhesion of myeloid cells (e.g., neutrophilic granulocytes) to cytokine-activated endothelial cells (Bevilacqua et al., Proc. Natl. Acad. Sci USA 84:9238, 1987). It has been suggested that ELAM-1 is involved in the regulation of inflammatory and immunological events at the interface of the blood and the blood vessel wall (Bevilacqua et al., Science 243:1160, 1989).